# Nuclear pore regulation of leukemia cell metabolism and survival

> **NIH NIH R21** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $273,488

## Abstract

PROJECT SUMMARY
The transport of molecules in and out of the nucleus is an essential cellular process that occurs through
multiprotein channels called nuclear pore complexes (NPCs). By controlling the exchange of proteins and RNAs
across the nuclear envelope, NPCs have an indirect control of gene regulation that strongly impacts many
processes including cell growth and proliferation. NPCs also regulate chromatin organization, DNA repair and
DNA replication and, thus, play an important function in the maintenance of genome integrity. Having such critical
roles in cellular homeostasis it is not surprising that many cancer cells show alterations in NPCs and their
components. But, even though abnormalities in NPCs have long been observed cancer cells, how this these
alterations affect nuclear pore function and whether they contribute to malignant transformation is mostly
unknown. Understanding how alterations in NPCs affect cellular function is a critical step towards establishing
how changes in the nuclear transport machinery are exploited to favor malignant transformation. Our previous
work uncovered that the tissue-specific NPC component Nup210 acts as an anti-apoptotic factor in specific cell
types, including muscle cells, neurons and T lymphocytes. We have identified that several leukemias show an
up-regulation of this tissue-specific NPC component, and that Nup210 is important for leukemic transformation.
We hypothesize that increased levels of Nup210 provide transformed hematopoietic cells with a survival
advantage that contributes to leukemogenesis. In this proposal we seek to uncover how Nup210 promotes cell
survival and leukemic transformation by characterizing its role in the regulation of leukemia cell metabolism
(Aim1), and by establishing the signaling/survival pathways regulated by Nup210 in these cells (Aim 2). Besides
offering a novel perspective on nuclear pore complex function and providing evidence on the molecular
mechanisms exploited by these structures to promote cancer cell survival, we expect our work will result in the
identification of specific differences between the nuclear transport machinery of normal and cancer cells that
could lead to the development of new anti-cancer therapies.

## Key facts

- **NIH application ID:** 9851271
- **Project number:** 1R21CA244028-01
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Marcela Raices
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $273,488
- **Award type:** 1
- **Project period:** 2019-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851271

## Citation

> US National Institutes of Health, RePORTER application 9851271, Nuclear pore regulation of leukemia cell metabolism and survival (1R21CA244028-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9851271. Licensed CC0.

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